THE TAMILNADU DR.M.G.R. MEDICAL UNIVERSITY · 2019. 11. 21. · like diplopia, fatigue and...

PREVALENCE OF NONMOTOR FEATURES ACROSS THE VARIOUS STAGES OF IDIOPATHIC PARKINSON’S DISEASE

AND ITS CORRELATION WITH THE SEVERITY AND DURATION OF THE DISEASE

Submitted in partial fulfillment of the requirements towards the conferment of

BRANCH - I D.M. NEUROLOGY

of

T H E T A M I L N A D U

D R . M . G . R . M E D I C A L U N I V E R S I T Y

C H E N N A I , T A M I L N A D U

AUGUST 2010

INSTITUTE OF NEUROLOGY MADRAS MEDICAL COLLEGE

CHENNAI – 600 003.

CERTIFICATE

This is to certify that this dissertation entitled

“PREVALENCE OF NONMOTOR FEATURES ACROSS THE

VARIOUS STAGES OF IDIOPATHIC PARKINSON’S DISEASE

AND ITS CORRELATION WITH THE SEVERITY AND

DURATION OF THE DISEASE” submitted by Dr.N.Shobana

appearing for D.M., Degree examination in August 2010 is a

bonafide record of work done by her under my direct guidance and

supervision in partial fulfillment of regulations of the Tamil Nadu

Dr. M.G.R. Medical University, Chennai. I forward this to the

Tamil Nadu Dr.M.G.R. Medical University, Chennai, Tamil Nadu,

India.

Prof. V. Sundar MCh Prof. R. M .Boopathy MD DM PROFESSOR & HEAD PROFESSOR of NEUROLOGY INSTITUTE OF NEUROLOGY INSTITUTE OF NEUROLOGY Madras Medical College & GGH Madras Medical College &GGH Chennai-600 003 Chennai-600 003

Dr. J. Mohanasundaram M.D, Ph.D. DNB DEAN Madras Medical College & Govt General Hospital Chennai – 600 003.

DECLARATION

I Dr. N. Shobana do solemnly affirm that this dissertation titled

“PREVALENCE OF NONMOTOR FEATURES ACROSS THE VARIOUS

STAGES OF IDIOPATHIC PARKINSON’S DISEASE AND ITS

CORRELATION WITH THE SEVERITY AND DURATION OF THE

DISEASE” is done by me at Institute of Neurology, Madras Medical

College & Govt. General Hospital, Chennai, during 2008-2010 under the

guidance and supervision of Prof.R.M.Boopathy M.D., D.M.,

Professor of Neurology, Institute of Neurology.

The dissertation is submitted to The Tamilnadu Dr. M.G.R.

Medical University towards the partial fulfillment of requirements for

the award of D.M., Degree in Neurology.

Place: Chennai

Date: 25.05.2010

N. Shobana

SPECIAL ACKNOWLEDGEMENT

I gratefully acknowledge and sincerely thank

Dr. J. Mohanasundaram M.D. Ph.D., DNB Dean Madras Medical

College, Chennai for permitting me to do this Dissertation and utilize

the Institutional facilities.

ACKNOWLEDGEMENT

My sincere thanks to Prof. V. Sundar, Professor and Head,

Institute of Neurology for his immense kindness in allowing me to

use the services of the department.

I thank Prof.R.M.Boopathy, Professor of Neurology,

Institute of Neurology, with profound gratitude for his constant

guidance, motivation, advice and valuable criticism, kindness and

encouragement which enabled me to complete this work.

I thank Prof. A.V.Srinivasan, Pro.V.Natarajan, former

Professors, Prof. C. Mutharasu, Prof. K.Bhanu,

Prof. Gopinathan, Professors, Institute of Neurology for their

constant guidance and encouragement.

I thank with gratitude, Dr. V. Kamaraj, Dr.S.Arunan,

Dr. M. Jawahar and Dr.P.Muthukumar for their constant

encouragement.

I thank my postgraduate friends for their constant support, all

the technical & non technical staffs of the Institute of Neurology,

for their cooperation.

Last but the most, I thank each of my patients for cooperating

for the study in spite of their pain and suffering.

CONTENTS

1. INTRODUCTION 1

2. AIM OF THE STUDY 3

3. MATERIALS AND METHODS 4

4. REVIEW OF LITERATURE 6

5. RESULTS 42

6. DISCUSSION 48

7 CONCLUSION 52

8 BIBLIOGRAPHY

PROFORMA

MASTER CHART

1

INTRODUCTION

Non motor symptoms(NMS) in Parkinson’s Disease constitutes a

major clinical challenge, as they are common, yet often overshadowed by

the dominance of motor symptoms and high awareness of these among

treating health care professionals. The NMS of PD were recognised by

James Parkinson himself. Thus in his essay on the shaking Palsy in 1817,

he referred to sleep disturbances, dysathria, constipation, dysphagia,

sialorhoea, urinary incontinence, constant sleepiness with slight delirium.

Since then numerous studies have indicated that NMS are frequent

accompaniments of PD affecting memory, bladder and bowel and sleep

among others. These NMS significantly affect the quality of life and may

precipitate hospitalization. Although common the NMS of PD are not

well recognised in clinical practice. While some such as depression,

dementia, autonomic and sleep disturbances are well known, others such

as dysphagia, dribbling of saliva, weight changes, sexual problems and

diplopia are less well recognised.

The NMS include neuropsychiatric symptoms, sleep disorders,

autonomic symptoms, sensory symptoms and miscellaneous symptoms

like diplopia, fatigue and seborhea. The nonmotor symptoms

questionnaire (NMS Quest) and the nonmotor symprom scale (NMSS)

were developed to assess the frequency and severity of NMS in PD

patients across all stages. The NMS Quest was validated in march 2007

2

by the Movement Disorder Society. It covers 9 domains and includes 30

items, including sleep / fatigue, cardiovascular, mood/cognition,

perceptual problems, attention / memory, gastrointestinal, urinary, sexual

functions and miscellaneous. The NMS Quest does not provide an overall

score or disability and is not a graded rating instrument. It is a screening

tool designed to draw attention to the presence of NMS and to initiate

further investigation.

Recent studies using the NMS Quest for PD patients have

highlighted the significant occurrence of a range of different NMS in PD

patients. Further studies validating the nonmotor symptom scale (NMSS)

also indicated a strong relationship between the burden of NMS in PD

and health related quality of life (QOL).The development of tools such

as the NMS Quest and NMSS alongside the revamped UPDRS which

includes a specific nonmotor domain will help define research and

therapy to improve the recognition and managememt of NMS of PD.

3

AIMS AND OBJECTIVES

1. To study the prevalence of nonmotor features across the various

stages of Idiopathic Parkinson’s Disease and

2. To correlate it with the severity and duration of the disease.

4

MATERIALS AND METHODS

Patients with Idiopathic Parkinson’s Disease who attend the

Movement Disorder clinic at the Institute of Neurology were studied. A

detailed and complete neurological examination was done. Imaging, CT

and MRI brain was done to exclude Parkinson Plus syndromes and

vascular parkinsonism. The patients were in the age group of more than

50 years and the disease duration varied between less than 5 years,5 to 10

years and more than 10 years. The motor symptoms were assessed

through the Unified Parkinson’s Disease Rating Scale(UPDRS) and the

disease staged according to the Hoehn and Yahr staging from stage 0 to

stage 5.The nonmotor features were assessed through the Nonmotor

Symptoms Questionnaire(NMS QUEST) which contains 30 items. This

included cognitive dysfunction,sleep disorders,autonomic abnormalities,

fatigue and depression. The prevalence of these Nonmotor symptoms

across the various stages of the disease was studied and its correlation

with the disease severity and duration assessed.

INCUSION CRITERIA:

1 Idiopathic Parkinson’s Disease patients with the age of onset of the

disease at 50 years and above

5

EXCLUSION CRITERIA:

1. Young onset Parkinson’s Disease(YOPD) with the age of onset

below 50 years

2. Parkinson’s Plus Syndromes like Progressive Supranuclear

Palsy(PSP), Multi System Atropy (MSA), Corticobasal

Degeneration(CBD)

3. Patients with Vascular Parkinsonism.

6

REVIEW OF LITERATURE

Parkinson’s Disease (also known as Parkinson disease or PD) is a

degenerative disorder of the central nervous system that often impairs the

sufferer's motor skills, speech, and other functions. It is characterized by

muscle rigidity, tremor, a slowing of physical movement (bradykinesia)

and a loss of physical movement (akinesia) in extreme cases. The primary

symptoms are the results of decreased stimulation of the motor cortex by

the basal ganglia, normally caused by the insufficient formation and

action of dopamine, which is produced in the dopaminergic neurons of

the brain. Secondary symptoms may include high level cognitive

dysfunction and subtle language problems. PD is both chronic and

progressive. PD is the most common cause of chronic progressive

parkinsonism, a term which refers to the syndrome of tremor, rigidity,

bradykinesia and postural instability. PD is also called "primary

parkinsonism" or "idiopathic PD". While many forms of parkinsonism are

"idiopathic", "secondary" cases may result from toxicity most notably of

drugs, head trauma, or other medical disorders. The disease is named

after English apothecary James Parkinson, who made a detailed

description of the disease in his essay: "An Essay on the Shaking Palsy"

(1817).

The term Parkinsonism is used for symptoms of tremor, stiffness,

and slowing of movement caused by loss of dopamine. "Parkinson's

7

disease" is the synonym of "primary parkinsonism", i.e., isolated

parkinsonism due to a neurodegenerative process without any secondary

systemic cause. In some cases, it would be inaccurate to say that the

cause is "unknown", because a small proportion is caused by genetic

mutation.

ETIOLOGY:

Most people with Parkinson's disease are described as having

idiopathic Parkinson's disease. There are far less common causes of

Parkinson's disease including genetic, toxins, head trauma, cerebral

anoxia, and drug-induced Parkinson's disease.

Genetic; Someone who has Parkinson's disease is more likely to

have relatives that also have Parkinson's disease. However, the

inheritance of Parkinson's disease is usually complex and not due to a

single gene defect. A number of specific genetic mutations causing

Parkinson's disease have been discovered. Genes identified as of 2008 are

Alpha-synuclein (SNCA), ubiquitin carboxy-terminal hydrolase L1

(UCH-L1), parkin (PRKN), leucine-rich repeat kinase 2 (LRRK2 or

dardarin) , PINK 1 and DJ-1.With the exception of LRRK2 they account

for a small minority of cases of PD.

Toxins; One theory holds that many or even most cases of the

disease may result from the combination of a genetically determined

vulnerability to environmental toxins along with exposure to those toxins.

8

The toxins most strongly suspected at present are certain pesticides and

transition-series metals such as manganese or iron, especially those that

generate reactive oxygen species, and/or bind to neuromelanin.In a

longitudinal investigation, individuals who were exposed to pesticides

had a 70% higher incidence of PD than individuals who were not

exposed.

Head trauma; Head trauma is considered a risk factor for PD since

past episodes are reported more frequently by individuals with

Parkinson's disease than by others in the population.

PATHOPHYSIOLOGY:

Dopaminergic pathways of the human brain in normal condition

(left) and Parkinson's disease (right). Red Arrows indicate suppression of

the target, blue arrows indicate stimulation of target structure.

The symptoms of Parkinson's disease result from the greatly

reduced activity of pigmented dopamine-secreting (dopaminergic) cells in

the pars compacta region of the substantia nigra. These neurons project to

9

the striatum and their loss leads to alterations in the activity of the neural

circuits within the basal ganglia that regulate movement, in essence an

inhibition of the direct pathway and excitation of the indirect pathway.

The direct pathway facilitates movement and the indirect pathway

inhibits movement, thus the loss of these cells leads to a hypokinetic

movement disorder. The lack of dopamine results in increased inhibition

of the ventral anterior nucleus of the thalamus, which sends excitatory

projections to the motor cortex, thus leading to hypokinesia.There are

four major dopamine pathways in the brain; the nigrostriatal pathway,

referred to above, mediates movement and is the most conspicuously

affected in early Parkinson's disease. The other pathways are the

mesocortical, the mesolimbic, and the tuberoinfundibular. Disruption of

dopamine along the non-striatal pathways likely explains much of the

neuropsychiatric pathology associated with Parkinson's disease.

The mechanism by which the brain cells in Parkinson's are lost

may consist of an abnormal accumulation of the protein alpha-synuclein

bound to ubiquitin in the damaged cells. The alpha-synuclein-ubiquitin

complex cannot be directed to the proteasome. This protein accumulation

forms proteinaceous cytoplasmic inclusions called Lewy bodies. The

latest research on pathogenesis of disease has shown that the death of

dopaminergic neurons by alpha-synuclein is due to a defect in the

machinery that transports proteins between two major cellular organelles

— the endoplasmic reticulum (ER) and the Golgi apparatus.

10

Excessive accumulations of iron, which are toxic to nerve cells, are also

typically observed in conjunction with the protein inclusions. Iron and

other transition metals such as copper bind to neuromelanin in the

affected neurons of the substantia nigra. Neuromelanin may be acting as a

protective agent. The most likely mechanism is generation of reactive

oxygen species. Iron also induces aggregation of synuclein by oxidative

mechanisms.Similarly, dopamine and the byproducts of dopamine

production enhance alpha-synuclein aggregation. The precise mechanism

whereby such aggregates of alpha-synuclein damage the cells is not

known.

CLINICAL FEATURES:

MOTOR; Four symptoms are considered cardinal in PD: tremor,

rigidity, bradykinesia and postural instability.

Tremor; normally has a frequency between 4 and 6 Hz (cycles per

second) and is the most apparent and well-known symptom. It is most

commonly a rest tremor, maximal when the limb is at rest and

disappearing with voluntary movement and sleep. It is a pronation-

supination tremor that is described as "pill-rolling". Tremor affects to a

greater extent the most distal part of the extremity and is typically

unilateral at onset. Though around 30% of PD sufferers do not have

tremor at disease onset most of them would develop it along the course of

the disease.

11

Rigidity: defined as joint stiffness and increased muscle tone. In

combination with a resting tremor, this produces a ratchety, "cogwheel

rigidity" when the limb is passively moved. It may be associated with

joint pain, such pain being a frequent initial manifestation of the disease.

Bradykinesia and Akinesia: the former refers to slowness of

movement while the latter to the absence of it. It is the most characteristic

clinical feature of PD and it produces difficulties not only with the

execution of a movement but also with its planning and initiation. The

performance of sequential and simultaneous movements is also hindered.

Rapid, repetitive movements produce a dysrhythmic and decremental loss

of amplitude.

Postural Instability: failure of postural reflexes, along other disease

related factors such as orthostatic hypotension or cognitive and sensory

changes, which lead to impaired balance and falls.It usually appears in

the late stages of PD.

Other motor symptoms include:

Gait and posture disturbances: Shuffling gait: gait is characterized

by short steps, with feet barely leaving the ground. Small obstacles tend

to cause the patient to trip. Decreased arm-swing.

12

Turning "en bloc": rather than the usual twisting of the neck and

trunk and pivoting on the toes, PD patients keep their neck and trunk

rigid, requiring multiple small steps to accomplish a turn.

Camptocormia: stooped, forward-flexed posture. In severe forms,

the head and upper shoulders may be bent at a right angle relative to the

trunk.

Festination: a combination of stooped posture, imbalance, and

short steps. It leads to a gait that gets progressively faster and faster, often

ending in a fall.

Gait freezing: also called motor blocks, is a manifestation of

akinesia. Gait freezing is characterized by a sudden inability to move the

lower extremities which usually lasts less than 10 seconds. It may worsen

in tight, cluttered spaces, when attempting to initiate gait or turning

around, or when approaching a destination. Freezing improves with

treatment and also with behavioral techniques such as marching to

command or following a given rhythm.

Dystonia: abnormal, sustained, painful twisting muscle

contractions, often affecting the foot and ankle (mainly toe flexion and

foot inversion) which often interferes with gait.

13

Speech and swallowing disturbances; Hypophonia: soft speech.

Monotonic speech: Speech quality tends to be soft, hoarse, and

monotonous. Festinating speech: excessively rapid, soft, poorly-

intelligible speech. Drooling: most likely caused by a weak, infrequent

swallow. Dysphagia; paired ability to swallow; which in the case of PD is

probably related to an inability to initiate the swallowing reflex or by a

too long laryngeal or oesophageal movement. Can lead to aspiration

pneumonia.

Other motor symptoms: Fatigue, Hypomimia:a mask-like face,

Difficulty rolling in bed or rising from a seated position. Micrographia:

small, cramped handwriting. Impaired fine motor dexterity and motor

coordination. Impaired gross motor coordination. Akathisia: an

unpleasant desire to move. Reemergence of primitive reflexes.

NONMOTOR SYMPTOMS:

Neuropsychiatric symptoms; Depression, apathy, anxiety, panic

attacks, anhedonia, attention deficit. hallucination, illusion, delusion

(disease or drug induced). Dementia, confusion or delirium (disease

and/or drug induced). obsessional and impulsive behaviour(usually drug

induced), repetitive behaviour (punding).

Sleep Disorders: Restless legs, Periodic Limb Movements, REM

behaviour disorder excessive daytime somnolence. Non REM sleep

related Disorder, vivid dreaming, insomnia.

14

Autonomic symptoms; Bladder disturbances; urgency, nocturia,

frequency, hyperhidrosis orthostatic hypotension; Vcoat hanger pain.

Sexual dysfunction; hypersexuality, erectile dysfunction, loss of libido.

Dry eyes (xerophthalmia) or wet eyes (lacrimation), dry mouth

(xerostomia), dribbling of saliva (sialorrhoea).

Gastrointestinal symptoms;(overlap with autonomic)include

delayed gastric emptying, ageusia, dysphagia, choking, reflux. vomiting,

nausea (usually drug related), constipation, anismus, volvulus,

megacolon. incomplete voiding of bowel, faecal incontinence.

Sensory symptoms; are pains, paraesthesia, olfactory disturbance

(hyposmia).

Miscellaneous symptoms; like fatigue, diplopia, blurred vision,

seborrhoea, weight loss.

Fluctuation related NMS; include pain, mental clouding, anxiety,

panic attacks, depression, hallucination, psychosis, screaming,

hyperventilation, hypoventilation. Hyperhidrosis, temperature changes,

somnolence, restless legs, akathisia. Belching, dysphagia, constipation,

anismus, urinary voiding difficulty, altered blood pressure.

A common misconception is that NMS occur only in late or

advanced PD. However NMS can first present at any stage of the disease.

Several NMS of PD such as olfactory dysfunction, constipation,

15

depression and erectile dysfunction may predate the motor signs,

symptoms and diagnosis of PD by a number of years.NMS may appear

early in the course of PD and become prominent as the disease

progresses, often dominating the later stages of the diseases. It is likely

that some NMS such as olfactory dysfunction in combination with other

symptoms such as REM behavioural disorder or constipation may form

part of a battery of tests to identify a population at risk of PD, which will

be particularly important if and when neuroprotective therapies become

available.

Stacy et al found that NMS were common even in patients within 5

years of (motor)disease arrest and they were captured much more

frequently with the use of a patient completed Questionnaire (NMS

QUEST)than simply in the course of a routine clinic appraisal, including

the questions in the Unified Disease Rating Scale(UPDRS). Recent

studies using the nonmotor symptoms questionnaire for PD (NMS Quest)

have highlighted the significant occurrence of a range of 30 different

NMS in PD in comparison with an age matched control group. These

occurred across a range of PD patients from early to advanced disease,

correlating strongly with advancing disease. In particular many NMS

such as dribbling saliva, dysphagia, sexual problems and pain had not

been discussed with the doctor before being flagged up by the NMS

Quest. The study also highlighted that, irrespective of county of study and

disease stage, most PD patients are likely to flag up 9 to 12 different

16

NMS in the NMS Quest at clinic visit. Additionally, further studies

validating the first dedicated scale for NMS of PD, the Parkinson’s

Disease Nonmotor Scale(NMSS)also indicated a strong relationship

between the burden of NMS in PD and health related QoL.

Most NMS are thought to be refractory to current dopaminergic

treatment, although this has not been assessed and this view is

increasingly challenged. For example, some dopaminergic agonists have

been reported to improve depression, REM behaviour and nocturia and

apomorphine may help erectlie dysfunction and anismus in PD.

Dopominergic agents can alleviate the ‘off’ period related NMS of PD,

such as pain, anxiety and depressed mood. In particular the rapid and

reliable onset of action of apomorphine injection or booster can transfer

the lives of subjects whose off NMS dominate their lives.

However many NMS may need specific targeted non-dopaminergic

treatment and the development of successful therapies for NMS will

depend upon accurate reproducible and robust means of quantification, an

understanding of their prevalence and evolution with disease progression

and their effect on QoL.

17

DIAGNOSIS:

The diagnosis is based on medical history and neurological

examination conducted by interviewing and observing the patient in

person using the Unified Parkinson's Disease Rating Scale.

The UPDRS is a scale that was developed as an effort to

incorporate elements from existing scales to provide a comprehensive but

efficient and flexible means to monitor PD-related disability and

impairment. The scale itself has four components, largely derived from

preexisting scales that were reviewed and modified by a consortium of

movement disorders specialists (Part I, Mentation, Behavior and Mood;

Part II, Activities of Daily Living; Part III, Motor; Part IV,

Complications).The UPDRS is often accompanied by and reported with

such scales as the Schwab and England and Hoehn and Yahr scales, these

latter scales are not part of the UPDRS per se. The strengths of the

UPDRS are many, and the scale provides a relatively comprehensive

assessment of motor aspects of PD. Extensive clinimetric analyses have

already been conducted on the UPDRS, providing it both scientific and

clinical credibility. The UPDRS is less comprehensive in its assessment

of nonmotor features of the disease.

18

HOEHN and YAHR STAGE:

STAGE O- No signs of disease

1- Unilateral disease

1.5- Unilateral plus axial involvement

2.0- Bilateral disease, without impairment of balance

2.5- Mild bilateral disease, with recovery on pull test

3.0- Mild to moderate bilateral disease, some postural

instability, physically independent

4.0- Severe disability, still able to walk or stand unassisted

5.0- Wheelchair bound or bedridden unless aided

IMAGING:

SPECT, FDGPET and fMRI scans are used for diagnosing

Parkinson's Disease. Due to this, the disease can be difficult to diagnose

accurately, especially in its early stages. Due to symptom overlap with

other diseases, only 75% of clinical diagnoses of PD are confirmed to be

idiopathic PD at autopsy. Early signs and symptoms of PD may

sometimes be dismissed as the effects of normal aging. The physician

may need to observe the person for some time until it is apparent that the

symptoms are consistently present. However, CT and MRI brain scans of

people with PD usually are normal.

19

TREATMENT:

Parkinson's disease is a chronic disorder that requires broad-based

management including patient and family education, support group

services, general wellness maintenance, physiotherapy, exercise, and

nutrition. At present, there is no cure for PD, but medications or surgery

can provide relief from the symptoms.

LEVODOPA: Levodopa remains the most effective medication to

improve motor features of PD with the fewest short-term side effects. It

effectively ameliorates bradykinesia and rigidity but is variably effective

for tremor. Levodopa is combined with the peripheral dopa decarboxylase

inhibitor carbidopa to reduce the peripheral metabolism of levodopa to

dopamine. This reduces nausea and increases levodopa delivery to the

brain, where it is converted to dopamine, stored, and slowly released by

remaining dopaminergic neurons.

Carbidopa / levodopa, now available generically, is available as

immediate release ([IR] 10/100, 25/100, and 25/250)and controlled

release ([CR] 25/100 and 50/200) formulations. Carbidopa / levodopa IR

and CR are also available as generics. The initial target dose is typically

carbidopa / levodopa IR 25/100administered 3 or 4 times per day, or

carbidopa / levodopa CR 50/200 twice a day, although these are more a

matter of convention than scientific rigor. Starting carbidopa / levodopa

at a dosage of one-half tablet once a day and increasing the daily dose by

20

one-half tablet every week until the target dose is reached may be helpful

to avoid nausea. Although carbidopa / levodopa is usually administered

away from meals to achieve the most rapid onset of action and the most

reliable effect, if nausea does occur, it can often be reduced by having

patients take the dose immediately following a meal. Levodopa alone has

a half-life of approximately 60 minutes, and when given with carbidopa it

has a half-life of approximately 90 minutes.

As the disease progresses and more dopamine neurons are lost, the

duration of clinical benefit shortens to a few hours, and many patients

develop choreiform (twisting, turning) movements when levodopa-

derived dopamine in the brain is peaking (peak dose dyskinesias). The

use of carbidopa / levodopa CR in early disease may be more convenient

and require fewer daily doses, but it has not been found to reduce the

development of motor fluctuations and dyskinesia compared with

carbidopa/levodopa IR.

Parcopa is an orally disintegrating carbidopa / levodopa tablet that

dissolves within seconds after being placed on the tongue. Parcopa is

convenient for patients because it can be taken with or without water,

such as when traveling, and is especially helpful for patients who have

swallowing problems. After dissolving, Parcopa is carried in the saliva to

the proximal small bowel where it is absorbed. Three strengths of

Parcopa are available: carbidopa / levodopa 10/100, 25/100, and 25/250.

21

Parcopa was approved based on the demonstration of bioequivalence with

Sinemet IR and should provide the same clinical benefit and side effects.

COMT INHIBITORS: Levodopa is also metabolized peripherally

by catechol-O-methyltransferase(COMT) to produce 3-O-methyldopa

(3-OMD). Entacapone is a selective, reversible, peripherally acting

COMT inhibitor that is used in conjunction with carbidopa/levodopa to

extend the levodopa half-life and allow more levodopa to be delivered to

the brain over a longer time. Entacapone is approved as an adjunct to

carbidopa/levodopa in patients who experience end-of-dose wearing off.

Entacapone is customarily administered with each dose of

carbidopa/levodopa. Some patients will notice an orange or brown

discoloration of urine, saliva, or sweat.Diarrhea occurs in 4% to 10% of

patients treated with entacapone. Hepatotoxicity has not been found to

occur with entacapone use, and routine liver monitoring is unnecessary.

Stalevo is a combination of carbidopa, levodopa, and entacapone.

Stalevo provides a convenient option for patients who are taking

carbidopa / levodopa and entacapone tablets and may be easier to

swallow. Stalevo is recommended for use in patients who have end-of-

dose wearing off on carbidopa/levodopa IR . In these patients, switching

from carbidopa / levodopa to Stalevo is comparable to adding entacapone

but with a reduced pill burden. For patients with dyskinesia and those

taking greater than 600-mg levodopa per day it is recommended that

entacapone should first be added, and if dyskinesia increases, the

22

levodopa dosage can be reduced. Once stabilized on carbidopa / levodopa

plus entacapone, the patient can be switched to the comparable dose

Stalevo tablets.

Tolcapone is a selective, centrally and peripherally acting,

reversible COMT inhibitor that is used to reduce off time in patients with

motor fluctuations on carbidopa / levodopa. Tolcapone extends the

levodopa half-life more than entacapone, but because of the potentially

fatal side effect of hepatic failure, its use is reserved for patients who

cannot be adequately controlled with other PD medications. It is

recommended that patients provide written informed consent before the

medication is begun, and liver function tests should be monitored for at

least 6 months. The new recommendations indicate that liver function

tests (serum alanine aminotransferase and aspartate aminotransferase)

should be performed every 2 to 4 weeks during the first 6 months of

therapy and then periodically according to the clinical judgement of the

health care provider.

Patients should discontinue tolcapone if liver enzyme levels exceed

twice the upper limit of normal. The usual initial dosage is 100 mg 3

times a day (tid), and it can be increased to 200 mg tid if necessary.

Tolcapone should be discontinued if benefit is not observed.Controlled

trials indicate that tolcapone improves motor function while allowing

reductions in levodopa dosage. One study that evaluated the use of

tolcapone in PD patients with motor fluctuations found a daily reduction

23

in off time of 2.0 hours in patients taking 100 mg tid and 2.5 hours in

patients taking 200 mg tid compared with baseline. In comparison,

patients taking placebo had only a 0.3-hour reduction in daily off time.

The levodopa boosting effects of the addition of tolcapone are

usually evident the day it is added. The main side effect is an increase in

dyskinesia. This occurs to a greater extent with tolcapone than with

entacapone, and in patients with dyskinesias it is often helpful to reduce

the levodopa dose by 25% to 50% when tolcapone is added. Other

potential side effects include diarrhea in 10% of patients. The diarrhea

can be severe and is usually delayed for 4 to 12 weeks after initiation of

therapy and uncommon after 6 months.

DOPAMINE AGONISTS : DAs are effective as monotherapy in

early PD to improve motor symptoms and as adjuncts to levodopa in

patients with motor fluctuations to reduce off time. They directly

stimulate dopamine receptors in the striatum, have relatively long half-

lives and are less likely to cause motor complications than levodopa. The

oral DAs are less effective than levodopa as the disease progresses but

often provide adequate benefit as monotherapy for 1 to 3 years.

Additional potential side effects include sleepiness, hallucinations,

peripheral edema, hypersexuality, and pathological gambling.

Hallucinations generally occur in patients with underlying dementia.

Multiple clinical trials have demonstrated that initial treatment with a DA

24

to which levodopa can be added causes fewer motor fluctuations and

dyskinesia than treatment with levodopa alone.

Pramipexole is a nonergot D2/D3 synthetic aminobenzothiazole

derivative that is effective as monotherapy in early disease and as an

adjunct to levodopa in patients with motor fluctuations. In the

Comparison of the Agonist Pramipexole to Levodopa Regarding

Emergence of Motor Fluctuations in PD (CALM-PD) study, 301 patients

were randomized to receive initial treatment with pramipexole or

levodopa and were followed for 4 years. Open-label levodopa could be

added as necessary. At study endpoint, patients assigned to levodopa had

better motor function than those taking pramipexole. However, only25%

of patients initially treated with pramipexole exhibited dyskinesia

compared with 54% of patients initially treated with levodopa.

The usual maximum dose of pramipexole is 4.5 mg/d in three

divided doses. It is started at a dosage of 0.125 mg tid for a week and then

titrated to 0.5 mg tid. Further escalation can be undertaken as necessary.

Side effects include somnolence, hallucinations, cognitive dysfunction,

and edema. Recent reports indicate that pathological gambling may be

associated with DAs, especially pramipexole, usually at high doses. In

one review, the incidence of pathological gambling was 1.5% in patients

taking pramipexole (mean dosage 4.3 mg/d, range 2 mg/d to 8 mg/d),

compared with an overall incidence of 0.05% in patients with PD

regardless of therapy. Excessive shopping and hypersexuality are other

25

forms of impulse control disorders that may occur with DA use. Patients

should be warned about these behaviours when DAs are prescribed, and

DA dosages may need to be reduced, if these problems emerge.

Ropinirole is a non ergot DA with a strong affinity for D2

receptors. It is effective as monotherapy in early disease and as an adjunct

to levodopa in patients with motor fluctuations. One study of ropinirole as

monotherapy in patients with early PD found a 24% improvement in

motor function in patients taking ropinirole after 6 months compared

with a 3% worsening for those patients taking placebo. Ropinirole has

also been shown to reduce the development of dyskinesia in early PD

patients compared with treatment with levodopa. A 5-year study that

randomized patients to initial treatment with ropinirole or levodopa to

which levodopa could be added when necessary found that only 20% of

patients assigned to ropinirole developed dyskinesia, compared with 45%

of patients assigned to levodopa.

These findings indicate that initial dopaminergic treatment with

ropinirole leads to a lower incidence of dyskinesia, and levodopa can be

added when necessary to control motor symptoms as the disease

progresses. The recommended initial dosage for ropinirole is 0.25 mg 3

times daily (total 0.75 mg per day). This can be increased weekly by

0.25-mg increments at each dose. The daily dose can then be increased by

1.5 mg/d after week 4 on a weekly basis up to a dose of 9 mg/d, and then

by up to 3 mg/d weekly up to the recommended maximum total daily

26

dose of 24 mg/d. Side effects include somnolence, hallucinations,

peripheral edema, and rarely impulse control disorders.

Pergolide, an ergot DA with strong affinity for D2 receptors, is

effective in reducing motor symptoms in PD. Several studies have shown

that the use of pergolide permits a significant reduction in levodopa

dosage when it is used as adjunct therapy in patients with motor

fluctuations compared with placebo.

Pergolide is usually initiated at a dose of 0.05 mg for the first 2

days and increased by 0.1 mg/d or 0.15 mg/d every third day over the

next 12 days. Pergolide may then be increased by 0.25 mg/d every third

day until an optimal therapeutic dose is achieved. Pergolide is usually

aministered in divided doses 3 times per day, and the usual maximum

dosage is 3 mg/d to 4 mg/d. Studies have identified an increased

frequency of valvular heart disease in patients taking pergolide. This

appears to be a potential side effect of all ergot agonists, and the

mechanism is believed to be activation of 5-hydroxytryptamine 2B

(5-HT2B) receptors. It may therefore be appropriate to obtain early

echocardiograms on patients who are receiving pergolide.

Pleuropulmonary and retroperitoneal fibrosis can also rarely occur.

Apomorphine is a nonergot DA that is approved as a subcutaneous

injection to treat acute intermittent off and hypomobility states in PD as a

rescue medication. Originally introduced as a PD drug in the mid-20th

27

century, its use was initially limited by side effects, including marked

nausea. It is now administered with an antiemetic. When injected

subcutaneously, its onset of action is approximately 10 to 15 minutes with

the effect lasting from 90 to 120 minutes. Side effects of apomorphine

include nausea, somnolence, dyskinesia, vomiting, and yawning.

The appropriate dosage for each patient must be determined based

on clinical response and side effects. Advanced patients who are

considering apomorphine should be pretreated with the antiemetic

trimetho benzamide 300 mg tid orally for atleast 3 days. Patients then

visit the doctor’s office in the off state and receive a test dose of

apomorphine 2 mg subcutaneously. Orthostatic blood pressures are

measured at 20, 40, and 60 minutes following the first test dose. If the

2-mg dose reverses PD symptoms, this dose is prescribed. If no clinical

response occurs, a dose of 4 mg is administered 2 hours after the first

dose. If the patient experiences a good clinical response, he or she maybe

treated with a dose of 3 mg per injection and may increase this dosage by

1mg increments every few days as needed. Most patients respond to 3 mg

to 6 mg of apomorphine.

MAO-B INHIBITORS; Selegiline is a relatively selective,

irreversible monoamine oxidase type B (MAO-B) inhibitor that is

beneficial as an adjunct to levodopa for patients who have motor

fluctuations. It also has modest symptomatic benefit as monotherapy in

early PD and has generated interest in possible neuroprotective effects.

28

The Deprenyl and Tocopherol AntioxidativeTherapy of Parkinsonism.

(DATATOP) study demonstrated that selegiline monotherapy in early

disease provides modest symptomatic benefit and significantly delays the

need for levodopa. Oral selegiline is approved as an adjunct to levodopa

in patients who demonstrate a deteriorating response to treatment.

The recommended dosing is 5 mg with breakfast and lunch. Doses

later in the day may cause insomnia. At dosages above 10 mg/d, oral

selegiline begins to lose its specificity for MAO-B and should therefore

usually be avoided because of the risk of tyramine induced hypertensive

crisis. Selegiline is used with caution with selective serotonin reuptake

inhibitor(SSRI) antidepressants to avoid the serotonin syndrome

characterized by agitation, restlessness, rigidity, hyperreflexia, shivering,

autonomic instability,flushing, fever, nausea, diarrhea, diaphoresis,

myoclonus, coma, and rarely rhabdomyolysis and death. The Zydis

selegiline formulation is a wafer that dissolves and is absorbed in the

mouth, thereby bypassing hepatic first-pass metabolism. This method of

absorption may allow for higher plasma concentrations of selegiline

compared with oral selegiline before MAO-A in the gut is inhibited.

Rasagiline is an irreversible MAO-B inhibitor that has been shown

to effectively treat symptoms of PD when used as monotherapy in

patients with early PD and as an adjunct to levodopa in patients with

motor fluctuations. It appears to have greater symptomatic efficacy than

oral selegiline. Rasagiline provides neuroprotection in a number of cell

29

and animal models and is free of amphetamine metabolites, which have

been demonstrated to interfere with neuroprotective effects of selegiline.

Rasagiline was evaluated as monotherapy in early disease in the

Rasagiline Mesylate (TVP-1012) in Early Monotherapy for PD Out

patients (TEMPO) study. Results from the 6-month double-blind phase

demonstrated that rasagiline significantly improves Unified Parkinson

Disease Rating Scale (UPDRS) scores compared with placebo and that

side effects were similar to placebo. The trial also incorporated a

delayed-start component, and patients who initially received placebo for

the first 6 months were treated with rasagiline 2 mg/d for the next 6

months while rasagiline treated patients continued on it. After 1 year,

patients treated with rasagiline from the beginning of the study had less

worsening in total UPDRS scores compared with patients who started

rasagiline after 6 months of placebo. This result suggests that rasagiline

might have benefit in slowing disease progression,but further

investigation is needed.

Another trial, Parkinson’s Rasagiline: Efficacyand Safety in the

Treatment of off (PRESTO), evaluated the effect of rasagiline as adjunct

therapy in levodopa treated patients with motor fluctuations. Another

study found that both rasagiline once daily and entacapone administered

with each levodopa dose significantly decreased off time and increased

on time compared with placebo. Although no dietary restrictions were

included in the pivotal clinical trials, the USFDA has recommended that

30

patients on rasagiline avoid foods that are high in tyramine, such as

redwine, aged cheeses, and aged meats.

ANTICHOLINERGIC MEDICATIONS:Anticholinergic medica-

tions such as trihexyphenidyl and benztropine are effective for reducing

tremor in some patients but have little effect on bradykinesia and rigidity.

Their use is limited by side effects, including confusion,

hallucinations,dry mouth and eyes, urinary retention, ocular

accommodation abnormalities, sweating, and tachycardia. These drugs

must be used with caution in older adults and in patients with glaucoma.

AMANTIDINE : is an antiviral medication that provides mild

benefit in treating PD signs and symptoms. It also symptomatically

reduces levodopa-induced peak-dose dyskinesia. It may act by direct

stimulation of dopamine receptors and by inhibiting dopamine reuptake.

Amantadine is administered at a dose of 100 mg bid or tid. It should be

used cautiously in elderly patients and in those with dementia, as it can

cause or worsen hallucinations.

SURGERY AND DEEP BRAIN STIMULATION:

After decades of lesion therapy, it was discovered that chronic

electrical stimulation had significant and lasting benefits for the treatment

of movement disorders. Deep brain stimulation (DBS) was introduced in

1987 by Benabid and colleagues for the treatment of tremor in patients

with Parkinson’s disease (PD). A few short years after its introduction,

31

high-frequency stimulation (HFS) of the globus pallidus interna (GPi),

and later the subthalamic nucleus (STN), was noted to dramatically

improve the symptoms of idiopathic PD. DBS is now US Food and Drug

Administration (USFDA)-approved for the treatment of PD. The

treatment is now considered standard of care for a subset of medically

refractory patients with PD. DBS is often compared with brain lesioning

(pallidotomy, thalamotomy, subthalamotomy). The main advantages of

DBS over lesioning include reversibility of the procedure, the ability to

program the stimulator, and the ability to perform bilateral procedures

without inducing pseudobulbar and other deficits.

Currently STN and GPi are the preferred brain targets for the

treatment of medication-refractory PD. While each has advantages,

particularly in the treatment of specific symptoms, there remains no

consensus as to which target is superior. Both have the potential to

improve the cardinal features of PD, including tremor, bradykinesia,

rigidity, gait dysfunction, and postural instability. Additionally, both are

known to reduce on–off fluctuations, dyskinesias, and dystonia. While

some studies have concluded that STN DBS was slightly superior in

improving motor scores, tremor, and bradykinesia, others have not shown

significant differences.

The marked clinical improvement usually seen with bilateral STN

stimulation. Bilateral STN stimulation does seem to have an advantage

over GPi in allowing medication reduction, which can also indirectly

32

result in a long-term cost savings. Because of its smaller size, STN has on

average a lower voltage requirement, which may provide an advantage in

terms of improving battery life. Dyskinesia management, however, may

be slightly superior with GPi stimulation, which provides a more direct

anti dyskinetic effect.

Additionally, many mood and cognitive side effects have been

reported with STN DBS, and their presence has raised questions

regarding safety in individual patients, particularly elderly persons and

those with cognitive impairment. To date, no head-to-head trials on which

to base selection of target have been done. Both targets are USFDA

approved, and both are efficacious.

The thalamic target (ventralis intermedius nucleus or VIM) has

been found to be efficacious in alleviating PD tremor but has not been

effective in treating other PD symptoms, including bradykinesia, rigidity,

dyskinesias, and postural instability. VIM nucleus DBS has been

demonstrated to be superior inefficacy in improving activities of daily

living in comparison with unilateral thalamotomy for PD tremor,

although there may be reasons to opt for lesion therapy. Stimulation of

the thalamus has also been reported to result in delayed tremor rebound.

Long-lasting effect on tremor in PD with VIM nucleus DBS has been

demonstrated however, the lack of effect on other PD symptoms has

greatly curbed the use of this target for PD. Recent reports suggest the

paramedian pontine nucleus as a possible target for improvement of gait

33

in parkinsonian patients. If it can be shown that this target improves

levodopa-unresponsive gait symptoms, it may prove an important

consideration for future trials.

DBS has proven efficacy in the treatment of the major motor

symptoms of PD, including bradykinesia, rigidity, tremor, gait

dysfunction, and postural instability. Long-term studies have

demonstrated that the effects of DBS are sustained. Perhaps the most

important point to remember when considering the referral of a patient is

that only those symptoms that respond to levodopa(when the patient is in

the best optimized on state) will respond to DBS. The main exception to

this rule is medication-refractory tremor, which can be well controlled

with DBS. No consensus has been formed as to the appropriate timing for

DBS surgery, but, in general, the procedure should be reserved for

medication-responsive symptoms in non demented patients with PD, who

may also have tremor or on–off fluctuations. In practical terms, the

patient under consideration for a surgical referral should experience one

or several of the following difficulties:

Motor fluctuations are seen in advanced PD, usually following 5

years or more of dopaminergic therapy. Many types of fluctuations have

been described. The most common and the earliest to appear are wearing

off of medication doses (predictable worsening of the parkinsonism or

reaching the off state because the current dose‘ ‘wears off’’ prior to the

next scheduled dose of levodopa). As the disease progresses, these off

34

states may become more unpredictable, and doses may last for shorter

intervals. Patients may also experience delayed ons (the period between

ingesting the dose of levodopa and the appearance of its positive effects),

dose failures (when a dose of levodopa fails to produce any effect),

on–off state(fluctuating between the on and off states), or sudden offs (an

unpredictable off state that may be unrelated to the timing of the levodopa

dose). A 5-year follow-up study of DBS has shown significant

improvement in off-medication motor scores. Patients report a significant

portion of the waking day in an off-medication state.

Dyskinesias become disabling and limit levodopa dosage. DBS can

decrease the severity of disability related to dyskinesias. Quality of life is

severely affected as a result of PD, and patients have levodopa -

responsive symptoms. Quality of life scores have shown an improvement

with DBS in many studies. The disease itself might not be advanced, but

if the patient has disabling medication-refractory tremor (dopamine

agonists, anticholinergics, and combinations have been tried) affecting

activities of daily living, DBS may be indicated.

35

TREATMENT OF NONMOTOR SYMPTOMS:

SLEEP DISORDERS: Excessive daytime sleepiness; (EDS)

commonly occurs in PD and frequently adversely affects quality of

life.EDS can be caused by the disease itself, medications, or sleep

disorders. Predictors of EDS in PD include increasing age, advanced

disease, and higher dosages of dopaminergic medications. DAs in

particular are a common cause of EDS in patients with PD. Acareful

medication review and sleep history are warranted for patients with EDS.

If a medication that might be causing EDS is identified, it can be reduced

or discontinued as feasible. If no medication likely to cause sleepiness is

identified, if EDS persists despite medication adjustments, or if the sleep

history is suspicious for a sleep disorder, polysomnographic evaluation of

sleep should be undertaken. If no treatable sleep disorder is identified,

treatment with modafinil or other wake-promoting agents can be

considered. The dose range of modafinil in these studies was 200 mg/d to

400 mg/d.

Insomnia; can be treated by having the patient adhere to a

consistent sleep schedule, attempt to avoid daytime napping, and abstain

from alcohol, caffeine, tobacco, and other stimulants in the evening

hours. A review of all current medications is warranted to identify those

that might be causing insomnia, such as bronchodilators, stimulants,

antidepressants, and weight-loss medications. If night time awakenings

are related to parkinsonian motor symptoms, a bedtime dose of a DA,

36

carbidopa / levodopa CR, or carbidopa / levodopa-entacapone (Stalevo)

may be helpful. A carbidopa / levodopa IR dose may provide relief if the

patient awakens at night and cannot get back to sleep because

medications have worn off. If necessary, injections of subcutaneous

apomorphine may be considered. If insomnia is related to nocturia,

anticholinergic medications such as tolterodine at bedtime may be helpful

to reduce bladder spasms. Depression and anxiety should be treated.

Some patients may require the use of hypnotics, such as zolpidem, or

trazadone to treat insomnia.

VIVID DREAMS AND HALLUCINATIONS; Vivid dreams are

often a precursor to frank hallucinations. Hallucinations are usually

triggered by dopaminergic medications in patients with underlying

dementia. In such patients, it is usually helpful to reduce or eliminate

DAs and minor PD medications, including amantadine and perhaps

anticholinergics and MAO-B inhibitors. Hallucinations commonly

respond to the addition of an atypical neuroleptic such as quetiapine or

clozapine at bedtime. Quetiapine is usually the medication of choice

because unlike clozapine, blood monitoring is not required.

REM BEHAVIOUR DISORDER: RBD is characterized by loss of

atonia during REM sleep when dreaming occurs. This leads to an ‘‘acting

out of dreams,’’ including sleep talking, shouting, and intense, sometimes

violent, movements. Patients may inadvertently injure their bed partners

by punching or choking them. RBD has been reported in 25% to 50% of

37

patients with PD and can precede the onset of PD by several years.

Clonazepam can be used in dosages of 0.5 mg to 2.0 mg at bedtime to

treat RBD.

RESTLESS LEGS SYNDROME : Restless legs syndrome occurs

in approximately 20% of patients with PD.DAs, including ropinirole and

pramipexole, may be used to treat.

SLEEP APNEA: Obstructive sleep apnea occurs in about 20% of

patients with PD and is defined by intermittently absent or reduced

airflow during sleep despite respiratory effort. Treatment usually consists

of wearing an airflow mask (continuous positive airway pressure).

FATIGUE; Fatigue is characterized by a feeling of lack of energy.

Some patients appear to have fatigue related to depression and improve

with antidepressant treatment. Others may improve with initiation of

antiparkinsonian medications. Treatments for fatigue include modafinil

and other stimulants.

ORTHOSTATIC HYPOTENSION; Treatment consists of

adequate hydration with eight or more glasses of fluid each day, the

liberal addition of salt to the diet (up to 150 mEq to 250 mEq), and the

use of mineralocorticoids, such as fludrocortisone, to increase

intravascular volume. The initial dose of fludrocortisone is 0.1 mg once

or twice a day, which can be increased to 0.3 mg to 0.6 mg per day if

needed. Midodrine is a peripherally acting alpha1agonist that produces

38

arteriole and venous capacitance vessel vasoconstriction. The initial

dosage of midodrine is 2.5 mg twice a day(bid) or tid with a maintenance

doe of up to 30 mg/d to 40 mg/d in divided doses.

CONSTIPATION; PD have delayed colonic transit time compared

with non-PD controls as well as decreased basal anal sphincter pressures

and hypercontractile external sphincter response. The disease process

itself may affect the enteric nervous system as Lewy bodies have been

found in the myenteric plexus of the colon and in the dorsal group of the

nucleus intermediolateralis of the third sacral segment of the spinal cord.

A paradoxical contraction of the striated sphincter muscles during

defecation called anismus may occur in patients with PD and is

considered to be a focal dystonia.

Treatment of constipation in PD starts with dietary change to

include more fruits, vegetables, and bran products. Medications that

inhibit gastric motility and promote gastrointestinal dryness, such as

anticholinergics, should be discontinued as feasible. If this is ineffective,

medical management includes polyethyleneglycol, an osmotic agent that

softens the stool and increases the frequency of bowel movements by

causing water to be retained in the stool. The recommended dose is 17 g

or one heaping tablespoon of powder per day in 8 ounces of liquid. Stool

softeners can often help to relieve constipation in PD as well.

39

One controlled study found that tegaserod, a prokinetic agent,

provides modest improvement in constipation. Two open-label studies

found that mosapride, a selective 5-HT4 agonist, improves constipation,

but controlled studies are lacking. Lactulose may be needed for patients

with refractory constipation. For cases of anismus, botulinum toxin

injections may be considered(30 units of botulinum toxin into two sites

on the puborectalis muscle).

DYSPHAGIA; Patients with PD have increased oropharyngeal

transit time, and Lewy bodies have been found in the myenteric plexus in

the esophagus in dysphagic PD patients. Non–dopamine related

abnormalities in the pedunculopontine nucleus or related structures in the

medulla may also cause swallowing difficulties. optimal treatment with

levodopa can improve swallowing, although some patients may need to

eliminate hard foods from the diet. Liquids may need to be thickened, and

patients should swallow sitting upright.

URINARY INCONTINENCE : Patients with PD may experience

urinary incontinence. Detrusor hyperreflexia can result in urinary

frequency, urgency, and nocturia, and dopamine deficiency has been

implicated as a cause for urinary incontinence in PD. Patients who report

urinary incontinence should undergo a urological evaluation, including

cystometric studies, to exclude other causes of urinary symptoms.

Treatment options include a reduction in fluids in the evening to reduce

nocturia and anticholinergic medication such as tolterodine tartrate,

40

oxybutyninchloride, or propantheline bromide. Another option is the

intranasal administration of desmopressin at bedtime to decrease urine

production overnight.

DROOLING; Drooling in PD is caused by saliva pooling in the

mouth secondary to swallowing difficulties rather than an increased

production of saliva. Siallorhea can lead to aspiration. Treatment includes

anticholinergic medications, such as glycopyrrolate. For some patients,

increased dopaminergic therapy may reduce drooling by improving

swallowing.

SEXUAL DYSFUNCTION: Sexual dysfunction is a complex

problem in PD and can manifest as difficulty achieving or maintaining

erection, loss of sexual interest, or occasionally hypersexuality from

dopaminergic medications. Sexual dysfunction affects both men and

women with PD. Reports of sexual dysfunction warrant an evaluation by

a urologist and cessation of medications such as propranolol and other

antihypertensives that can contribute to the condition. Depression as a

possible cause of sexual dysfunction must also be addressed. Sildenafil, a

potent inhibitor of phosphodiesterase type 5, may be useful in treating

erectile dysfunction.

DEPRESSION: Depression is estimated to affect as many as 50%

of patients with PD and is more common than in age-matched non-PD

controls. Depression in PD is associated with dysphoria and sadness, and

less by self-blame and guilt. It may affect patients prior to the onset of

motor symptoms and may prove to be a preclinical marker of the disease.

41

The exact cause of depression in PD is unknown. Antidepressants,

including tricyclics and SSRIs, have been found to improve depression in

patients with PD, and the DA pramipexole may also have antidepressant

efficacy.

DEMENTIA; Dementia probably affects close to 40% of patients

with PD and usually emerges later in the course of the disease. Dementia

in PD is associated with longer disease duration and older age at onset

and is a risk factor for nursing home placement. Patients with dementia

have short-term memory deficits but may also have difficulty with verbal

fluency and personality and behavioral changes. Rivastigmine,

a cholinesterase inhibitor, is now approved for use in treating dementia in

PD. In a study of donepezil, at dosages of 5 mg/d to 10 mg/d,

improvements occurred in the Mini-Mental State Examination and

Clinical Global Impression scale compared with placebo. Galantamine

may also improve cognitive dysfunction in PD.

PSYCHOSIS; Occurs in 30% of patients. Unfortunately, many

medications that are used to treat motor dysfunction in PD, including

amantadine, DAs, and to a lesser extent anticholinergics, levodopa,

COMT inhibitors, and MAO-B inhibitors, can exacerbate psychosis and

may need to be discontinued or reduced if psychosis occurs. Quetiapine

and clozapine have less parkinsonian side effects than other atypical or

classical antipsychotics and are effective in treating psychosis symptoms,

usually at relatively low doses(12.5 mg/d to 150 mg/d for quetiapine and

12.5 mg/d to 75 mg/d for clozapine).

42

OBSERVATION & RESULTS:

This study included 100 patients with Idiopathic Parkinson’s

Disease.

AGE DISTRBUTION:

The number of patients in the

age group between 50 -60 years - 47

age group between 60-70 years - 41

age group > 70 years - 12

SEX DISTRIBUTION:

There were 75 males and 25 females.

43

DURATION OF DISEASE:

The number of patients with the

duration of the disease from 0-5 years - 73

duration of the disease from 5-10 years - 21

duration of the disease > 10 years - 6

44

STAGE OF DISEASE:

Based on the Hoehn and Yahr Staging;

number of patients in Stage 1 - 24

number of patients in Stage 1.5 - 7


number of patients in Stage 2.5 - 8



45

PREVALENCE OF NON-MOTOR SYMPTOMS IN THE STUDY

COHORT: The prevalence of NMS were;

Drooling-37%

Disturbances in taste and smell-27%

Swallowing difficulty-24%

Constipation-50%

Urgency-47%

Nocturia-58%

Dizziness-34%

Pains-28%

Dreams-23%

Insomnia-35%

Sleepiness-20%

Memory-33%

Anxiety-22%

Depression-34%

Hallucination-15%

Sexual Dysfunction-14%

Falls-24%

Restless leg syndrome-14%

Sweating-40%

Weight loss-16%

46

47

The prevalence of NMS across the various stages of Idiopathic

Parkinson’s disease are ;

The number of NMS in Stages 1 and 1.5 were less than 5(range of 2-3)

The number of NMS in Stages 2 and 2.5 were in the range of 5 and 7.

The number of NMS in Stages 3 and 4 were between 9 and 12.

The patients in Hoehn and Yahr Stages 1 to 1.5 had duration of

disease ranging between 6 months and 2 years. Those in Stages 2 and 2.5

had duration of disease between 2 and 5 years.Patients in Stages 3 and 4

had duration of disease ranging between 5 and 15 years.

48

DISCUSSION

Chaudhari K R,Martinez Martin P,Schapira AHV, et al (49) from

the Unit of Neuro Epidemiology of Carlos Institute of Health, Madrid,

Spain have done an International Multicentre Pilot Study of the first

comprehensive self completed non motor symptoms questionnaire for

Parkinson Disease. They have studied the prevalence of NMS in 545

patients using the NMS Quest. The results were Dribbling - 40%,

Disturbances in taste / smell-29%, swallow- 28%, constipation-

50%,urgency - 53%, nocturia - 60%, pains - 27%, memory-43%,

hallucination-20%, depression - 45%, anxiety - 42%, sexual dysfunction-

30%, dizziness-35%, falls - 25%, sleepiness - 29%, insomnia-43%,

dreams - 34%, RLS - 39%, sweating - 15%, weight loss - 15%.

Our study has shown higher prevalence of NMS like Nocturia

(58%), urgency (47%) and constipation(50%).This compares with

Chaudhari et al which has also shown higher prevalence of these

symptoms namely Nocturia (60%),urgency (53%) and constipation

(50%). The next prevalent NMS were Insomnia (35%), Depression

(34%) memory (33%), dreams (23%), anxiety (22%), sleepiness (20%)

and hallucinations (15%). These were less compared to Chaudhari et al

which has documented a higher prevalence of the same, namely Insomnia

(43%), memory (43%), Depression (45%) dreams (34%), anxiety (42%),

sleepiness (29%), hallucinations (20%).

49

Dizziness was reported in 34%,swallowing difficulty in 24%,falls

in 24% which has almost the same as reported by Chaudhari et al. Sexual

Dysfunction was reported in14% patients as against 30% by Chaudhari et

al. Sweating was prevalent in 40% as against 15% reported by Chaudhari

et al.RLS was reported in 14% which was 39% in Chaudhari at al. Pain

was prevalent in 28%,and weight loss in 16% which is same when

compared with Chaudhari et al.

The most prevalent NMS were Autonomic Symptoms namely

Nocturia urgency, constipation, sweating, dizziness and drooling. This

was followed by Neuropsychiatric symptoms like memory disturbances,

depression, anxiety and hallucinations and sleep disturbances which

include insomnia, sleepiness and dreams. Pains and weight loss were also

prevalent. Diplopia, delusions, bowel and bladder incontinence were

reported in a small percentage of patients.

The prevalence of NMS increased with the severity and duration of

the disease. The number of NMS ranged between 2 to 3 in stages 1 and

1.5, increased to 5 to 7 in stages 2 and 2.5 and ranged between 9 to 12 in

stages 3 and 4.The number of NMS were less when the duration of the

disease was less than 2 years and increased with the duration of the

disease. It was maximum reported when the duration of the disease was

more than 5 years.

50

In the Indian context, Prevalence of NMS in PD has been carried

out at NIMS, Hyderabad, Andhra Pradesh, India. Here the patients had

NMS scores between 6 to 20. The most common symptoms identified

were dribbling of saliva, swallowing difficulty, urinary urgency, sexual

dysfunction, unexplained pains, anxiety, dreams, insomnia, sweating,

memory disturbances and falls. Alteration in taste and smell, bowel and

urinary incontinence, change in weight and hallucinations were seen in

fewer patients.

In another study carried out at the Comprehensive Care Centre For

Movement Disorders, Sree Chitra Tirunal Institute for Medical Sciences

and Technology, Tiruvananthapuram, Kerala, NMS was assessed by the

NMS Scale (9 domains) in 100 consecutive PD patients. The Mood /

cognition domain was most frequently involved (84.2%), while the

cardiovascular domain was the least affected (22.4%). Four of the

domains namely, cardiovascular, perceptual problems, hallucinations,

gastrointestinal and urinary showed significant correlation with the

duration of the disease and severity of PD. There was a significant

correlation between the overall severity of NMS and duration of disease

and severity of PD.

Dagmar Verban etal (50) from the Department of Neurology,

Leiden University Medical centre, The Netherlands 2007 has

characterised these non motor domains in patients of the Profiling

Parkinson’s Disease (PROPARK) cohort and describes their relation with

51

other domains of the disease as well as their impact on disability and

quality of life. Of the domains evaluated olfaction is the only domain that

seemed unrelated to any of the other impairment domains. All other

nonmotor symptoms were related to symptoms of other domains. The

strongest relation was found between night time sleep problems and

depressive symptoms and between psychotic and autonomic symptoms.

The relation found between the different impairment domains may

emerge through different causes. First two domains may be related

because of a shared underlying mechanism that is inherent to the disease

or may be induced by medication or by a combination of both. Second a

relation between impairment domains may emerge because different

brain regions are simultaneously affected by the disease process. The

pathological staging system of Braak, in which the upper brainstem,

midbrain and limbic system become involved as the disease progresses,

may explain the co-occurrence of features from two different domains. Of

the nonmotor domains in PD depressive symptoms and autonomic

dysfunction were the most important contributors to HRQoL. Our study

has also demonstrated relation between insomnia and depression.

52

CONCLUSION

(1) Nonmotor symptoms are prevalent across all stages of Parkinson’s

Disease.

(2) The most prevalent ones were Autonomic which includes

Constipation, Nocturia, Urgency and sweating. This was followed

by insomnia, depression and memory disturbances. Dizziness,

Drooling, Falls and unexplained pains were also significantly

reported.

(3) The number of NMS increased as the disease severity progressed.

The number of NMS in stages 1 and 1.5 were the least. It increased

through stages 2 and 2.5 and were highest reported in stages 3

and 4.

(4) The number of NMS also correlated with the duration of the

disease. The number of NMS were least when the duration was less

than 2 years, increasing as the duration increased and maximum

reported when duration was more than 5 years.

BIBLIOGRAPHY

1. Jankovic J (April 2008). Parkinson's disease: clinical features and

diagnosis. Journal of Neurology, Neurosurgery and Psychiatry.

79 (4): 368–76.

2. Aarsland D, Brønnick K, Ehrt U, et al. (January 2007).

Neuropsychiatric symptoms in patients with Parkinson's disease

and dementia: frequency, profile and associated care giver stress.

Journal of Neurology, Neurosurgery and Psychiatry. 78 (1): 36–42.

3. Caballol N, Martí MJ, Tolosa E (September 2007). Cognitive

dysfunction and dementia in Parkinson disease. Movement

Disorders. 22 Suppl 17: S358–66.

4. Pfeiffer RF (February 2003). Gastrointestinal dysfunction in

Parkinson's disease. Lancet Neurology. 2 (2): 107–16.

5. Davie CA (2008). A review of Parkinson's disease.Br Med Bull.

86: 109–27.

6. Lesage S, Brice A (April 2009). Parkinson's disease: from

monogenic forms to genetic susceptibility factors.Hum Mol Genet

18 (R1): R48–59.

7. Di Monte DA, Lavasani M, Manning-Bog AB (October 2002).

Environmental factors in Parkinson's disease.Neurotoxicology. 23

(4-5): 487–502.

8. Jenner P (1998). Oxidative mechanisms in nigral cell death in

Parkinson's disease.Movement Disorders. 13 (Suppl 1): 24–34.

9. Chiueh CC, Andoh T, Lai AR, Lai E, Krishna G (2000).

Neuroprotective strategies in Parkinson's disease: protection

against progressive nigral damage induced by free radicals.

Neurotoxicity Research. 2 (2-3): 293–310.

10. Cotzias GC (January 1966). Manganese, melanins and the

extrapyramidal system. Journal of Neurosurgery. 24 (1):

Suppl:170 – 80.

11. Barbeau A (1984). Manganese and extrapyramidal disorders

(a critical review and tribute to Dr. George C. Cotzias).

Neurotoxicology. 5 (1): 13–35.

12. Ascherio A, Chen H, Weisskopf MG, et al. (August 2006).

Pesticide exposure and risk for Parkinson's disease. Annals of

Neurology. 60 (2): 197–203.

13. Goldstein DS, Sewell L, Holmes C (January 2010). Association of

anosmia with autonomic failure in Parkinson disease. Neurology.

74 (3): 245–51.

14. Chade AR, Kasten M, Tanner CM (2006). Nongenetic causes of

Parkinson's disease. J Neural Transm Suppl. (70): 147–51.

15. Rugbjerg K, Ritz B, Korbo L, Martinussen N, Olsen JH (2008).

Risk of Parkinson's disease after hospital contact for head injury:

population based case-control study.BMJ 337.

16. Spangenberg S, Hannerz H, Tüchsen F, Mikkelsen KL (January

2009). A nationwide population study of severe head injury and

Parkinson's disease.Parkinsonism Relat Disord.15 (1): 12–4.

17. Parkinson's Disease Mechanism Discovered, HHMI Research

News June 22, 2006.

18. Kaur D, Andersen JK (October 2002). Ironing out Parkinson's

disease: is therapeutic treatment with iron chelators a real

possibility?.Aging Cell 1 (1): 17–21.

19. Masliah E, Rockenstein E, Veinbergs I,et al (2000). Dopaminergic

loss and inclusion body formation in alpha-synuclein mice:

implications for neurodegenerative disorders.Science 287 (5456):

1265–9.

20. Chan CS, Guzman JN, Ilijic E,et al. (June 2007). Rejuvenation'

protects neurons in mouse models of Parkinson's disease.Nature

447 (7148): 1081–6.

21. Gelb DJ, Oliver E, Gilman S (January 1999). Diagnostic criteria

for Parkinson disease.Archieves of Neurology. 56 (1): 33–9.

22. R. Cilia et al. (2006). Long-term Efficacy of Entacapone in

Patients with Parkinson's Disease and Motor Fluctuations - A Six-

Year Clinical Follow-Up Study.Neurology;5728.

23. Pramipexole (Sifrol) for Parkinson’s disease: National Prescribing

Service Ltd NPS.

24. Goldenberg MM (October 2008). Medical management of

Parkinson's disease. P & T 33 (10): 590 – 6060.

25. Thorogood M, Armstrong B, Nichols T, Hollowell J (July 1998).

Mortality in people taking selegiline: observational study.BMJ 317

(7153): 252–4.

26. Marras C, McDermott MP, Rochon PA,et al. (January 2005).

Survival in Parkinson disease: thirteen-year follow-up of the

DATATOP cohort.Neurology 64 (1): 87–93.

27. Guridi J, Obeso JA (2001). The subthalamic nucleus,

hemiballismus and Parkinson's disease: reappraisal of a

neurosurgical dogma.Brain 124 (Pt 1): 5–19.

28. Fukuda M, Kameyama S, Yoshino M, Tanaka R, Narabayashi H

(2000). Neuropsychological outcome following pallidotomy and

thalamotomy for Parkinson's disease.Stereotactic and Functional

Neurosurgery 74 (1): 11–20.

29. Deane KH, Jones D, Playford ED, Ben-Shlomo Y, Clarke CE

(2001). Physiotherapy for patients with Parkinson's Disease: a

comparison of techniques.Cochrane Database of Systemic Reviews

(3): 2817.

30. Deane KH, Whurr R, Playford ED, Ben-Shlomo Y, Clarke CE

(2001). A comparison of speech and language therapy techniques

for dysarthria in Parkinson's disease.Cochrane Database of

Systemic Reviews (2): 2814.

31. Goodwin VA, Richards SH, Taylor RS, Taylor AH, Campbell JL

(April 2008). The effectiveness of exercise interventions for people

with Parkinson's disease: a systematic review and meta-

analysis.Movement Disorders 23 (5): 631–40.

32. Schulz GM (July 2002). The effects of speech therapy and

pharmacological treatments on voice and speech in Parkinson s

disease: a review of the literature.Current Medicinal Chemistry

(14): 1359–66.

33. Fox CM, Ramig LO, Ciucci MR, Sapir S, McFarland DH, Farley

BG (November 2006). The science and practice of LSVT/LOUD:

neural plasticity-principled approach to treating individuals with

Parkinson disease and other neurological disorders.Seminars in

Speech and Language 27 (4): 283–99.

34. Apaydin H, Ahlskog JE, Parisi JE, Boeve BF, Dickson DW

(January 2002). Parkinson disease neuropathology: later-

developing dementia and loss of the levodopa response.Archives of

Neurology 59 (1): 102–12.

35. Manyam BV, Sánchez-Ramos JR (1999). Traditional and

complementary therapies in Parkinson's disease.Advances in

Neurology 80: 565–74.

36. Parkinson J (2002). An essay on the shaking palsy. 1817. The

Journal of Neuropsychiatry and Clinical Neurosciences 14 (2):

223–36; discussion 222.

37. Berrios G.E. (1995). Parkinson's Disease". in Berrios G.E. and

Porter R.The History of Clinical Psychiatry. London: Athlone

Press. pp. 95–112.

38. Hornykiewicz O (2002). L-DOPA: from a biologically inactive

amino acid to a successful therapeutic agent.Amino Acids 23

(1-3): 65–70.

39. Cotzias GC (March 1968). L-Dopa for Parkinsonism". The New

England Journal of Medicine 278 (11): 630.

40. Chiueh CC, Wu RM, Mohanakumar KP et al. (November 1994). In

vivo generation of hydroxyl radicals and MPTP-induced

dopaminergic toxicity in the basal ganglia.Annals of the New York

Academy of Sciences 738: 25–36.

41. Orr, Leslie (February 10, 2005). PCBs, fungicide open brain cells

to Parkinson's assault. Medical News Today.

42. Manning-Bog AB, McCormack AL, Li J, Uversky VN, Fink AL,

Di Monte DA (January 2002). The herbicide paraquat causes

up-regulation and aggregation of alpha-synuclein in mice: paraquat

and alpha-synuclein.The Journal of Biological Chemistry 277 (3):

1641–4.

43. Thiruchelvam M, Richfield EK, Baggs RB, Tank AW, Cory-

Slechta DA (2000). The nigrostriatal dopaminergic system as a

preferential target of repeated exposures to combined paraquat and

maneb: implications for Parkinson's disease.J.Neurosci. 20 (24):

9207–14.

44. Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov

AV, Greenamyre JT (December 2000). Chronic systemic pesticide

exposure reproduces features of Parkinson's disease.Nature

Neuroscience 3 (12): 1301–6.

45. Kitazawa M, Anantharam V, Kanthasamy AG (December 2001).

Dieldrin-induced oxidative stress and neurochemical changes

contribute to apoptopic cell death in dopaminergic cells. Free

Radical Biology and Medicine 31 (11): 1473–85.

46. Corrigan FM, Wienburg CL, Shore RF, Daniel SE, Mann D

(February 2000). Organochlorine insecticides in substantia nigra in

Parkinson's disease. Journal of Toxicology and Environmental

Health 59 (4): 229–34.

47. Kaplitt MG, Feigin A, Tang C, Fitzsimons HL, Mattis P, Lawlor

PA, Bland RJ, Young D, Strybing K, Eidelberg D, During MJ

(2007). Safety and tolerability of gene therapy with an adeno-

associated virus (AAV) borne GAD gene for Parkinson's disease:

an open label, phase I trial. Lancet 369 (9579): 2097–105.

48. Bonuccelli U, Del Dotto P (2006). New pharmacologic horizons in

the treatment of Parkinson disease. Neurology 67 (2): 30–38.

49. Chaudhuri KR, Healy D, Schapira AHV. The non motor symptoms

of Parkinson’s Disease; Diagnosis and management. Lancet

Neurology 2006;(5);235-45.

50. Dagmar Verbaan, Johan Marinus, Martine Visser, Stephanic M.

Van Rooden, Non Motor Symptoms in Parkinson’s Disease.

Journal of Neurology, Neurosurgery and Psychiatry 2007 : (78) :

1182 – 1187.

MASTER CHART

S.No Age Sex Duration of Disease

UPDRS Score

Hoehn & Yahr

stage

NON-MOTOR SYMPTOMS

Dro

olin

g

Tas

te /

Smel

l

Swal

low

Con

stip

atio

n

Urg

ency

Noc

turi

a

Diz

zine

ss

Pain

s

Dre

ams

Inso

nmia

Slee

pine

ss

Mem

ory

Anx

iety

Dep

ress

ion

Hal

luci

natio

n

Sexu

al

dysf

unct

ion

Falls

RL

S

Swea

ting

Wei

ght L

oss

1 56 M 5 49 3 Y y y y y y y y y y y y2 66 M 2 30 1.5 y y y y 3 59 M 1 27 1 y y y 4 65 M 2 23 2 y y y y y 5 69 F 4 42 1.5 y y y y y 6 60 F 9 52 3 y y y y y y y y y y 7 62 M 4 41 2 y y y y y y 8 60 M 2 25 1.5 y y y 9 53 M 2 52 3 y y y y y y y y y y 10 64 F 6 54 3 y y y y y y y y y y 11 54 M 2 29 1 y y y 12 51 F 2 30 1 y y y 13 65 M 4 44 2 y y y y y14 50 F 7 49 3 y y y y y y y y y y y15 52 F 4 52 2 y y y y y 16 46 M 2 51 3 y y y y y y y y y y y 17 52 F 8 44 2 y y y y 18 51 M 3 33 2 y y y y y 19 56 M 8 53 3 y y y y y y y y y y y 20 63 M 1 24 1 y y y 21 72 M 3 31 2 y y y y y y 22 55 M 2 46 2 y y y y y


UPDRS Score

Hoehn & Yahr

stage

NON-MOTOR SYMPTOMS

Dro

olin

g

Tas

te /

Smel

l

Swal

low

Con

stip

atio

n

Urg

ency

Noc

turi

a

Diz

zine

ss

Pain

s

Dre

ams

Inso

nmia

Slee

pine

ss

Mem

ory

Anx

iety

Dep

ress

ion

Hal

luci

natio

n

Sexu

al

dysf

unct

ion

Falls

RL

S

Swea

ting

Wei

ght L

oss

23 59 M 2 42 2 y y y y y 24 52 M 1 33 1 y y 25 55 M 1.5 27 1 y y y 26 60 F 3 27 1 y y y 27 67 M 5 49 2 y y y y 28 55 M 3 48 2 y y y y y 29 61 M 5 55 3 y y y y y y y y y 30 66 M 3 31 2 y y y 31 58 M 1 26 1 y y y 32 68 M 5 36 3 y y y y y y y y y y 33 60 M 6 45 3 y y y y y y y y y y 34 73 M 3 52 3 y y y y y y y y y y y y 35 72 M 1 32 2 y y y y 36 78 F 2 37 2 y y y y 37 55 F 1 29 1 y y 38 62 M 1.5 32 1 y y y 39 78 M 1.5 63 2 y y y y y 40 60 M 1 22 1 y y y 41 55 M 3 43 2.5 y y y y y 42 62 M 2 42 2 y y y y 43 68 M 15 68 3 y y y y y y y y y y y 44 62 M 9 50 2.5 y y y y y y 45 56 F 2 36 1.5 y y y y y 46 60 M 4 60 2 y y y y y y y y y 47 70 M 3 79 3 y y y y y y y y y y y


UPDRS Score

Hoehn & Yahr

stage

NON-MOTOR SYMPTOMS

Dro

olin

g

Tas

te /

Smel

l

Swal

low

Con

stip

atio

n

Urg

ency

Noc

turi

a

Diz

zine

ss

Pain

s

Dre

ams

Inso

nmia

Slee

pine

ss

Mem

ory

Anx

iety

Dep

ress

ion

Hal

luci

natio

n

Sexu

al

dysf

unct

ion

Falls

RL

S

Swea

ting

Wei

ght L

oss

48 77 M 8 81 3 y y y y y y y y y y y y 49 58 M 4 61 2.5 y y y y y y y 50 62 M 8 61 3 y y y y y y y y y y 51 60 M 7 48 2 y y y y y y y 52 58 M 2 32 1 y y y y y 53 68 M 3 33 2 y y y y 54 52 M 1 34 1 y y y y y 55 62 M 2 32 1 y y y y y y 56 57 M 5 70 3 y y y y y y y y y y y y 57 70 M 1 54 2 y y y y 58 54 M 1.5 34 1 y y y 59 55 M 1 51 2 y y y y y 60 65 M 15 67 2.5 y y y y y y 61 65 F 13 109 4 y y y y y y y y y y y 62 52 F 2 59 2 y y y y y y 63 69 M 10 78 3 y y y y y y y y y 64 58 M 1 24 1 y y 65 60 M 2 40 2 y y y y 66 63 M 1.5 30 1.5 y y y y 67 70 M 8 89 3 y y y y y y y y y y 68 62 F 5 36 2 y y y y y 69 55 M 4 52 2.5 y y y y y 70 53 M 2 26 1 y y y 71 60 F 9 80 3 y y y y y y y y y y y y 72 70 M 4 38 2 y y y y y


UPDRS Score

Hoehn & Yahr

stage

NON-MOTOR SYMPTOMS

Dro

olin

g

Tas

te /

Smel

l

Swal

low

Con

stip

atio

n

Urg

ency

Noc

turi

a

Diz

zine

ss

Pain

s

Dre

ams

Inso

nmia

Slee

pine

ss

Mem

ory

Anx

iety

Dep

ress

ion

Hal

luci

natio

n

Sexu

al

dysf

unct

ion

Falls

RL

S

Swea

ting

Wei

ght L

oss

73 56 M 3 40 2 y y y y y 74 58 F 12 122 4 y y y y y y y y y y y 75 54 M 1 24 1 y y y 76 66 M 2.5 40 2 y y y y 77 52 F 1 28 1 y y y 78 71 M 6 92 3 y y y y y y y y y 79 55 M 4 64 2.5 y y y y y 80 57 F 2 30 1.5 y y y y 81 64 M 2 42 2 y y y y 82 58 M 5 102 3 y y y y y y y y y y 83 76 M 3 48 2 y y y y 84 52 F 1 28 1 y y y 85 65 M 0.5 26 1 y y 86 59 M 2.5 44 2 y y y y y 87 60 M 4 98 3 y y y y y y y y y 88 62 M 14 126 4 y y y y y y y y y 89 64 M 1 40 2 y y y 90 67 F 3 48 2.5 y y y y y y 91 54 F 1 22 1 y y y y 92 70 F 8 110 3 y y y y y y y y y y y 93 52 M 2.5 32 2 y y y y 94 55 M 1 24 1 y y y 95 60 M 2 46 2 y y y y y 96 56 F 3 50 2.5 y y y y y y 97 58 M 3 48 2 y y y y y


UPDRS Score

Hoehn & Yahr

stage

NON-MOTOR SYMPTOMS

Dro

olin

g

Tas

te /

Smel

l

Swal

low

Con

stip

atio

n

Urg

ency

Noc

turi

a

Diz

zine

ss

Pain

s

Dre

ams

Inso

nmia

Slee

pine

ss

Mem

ory

Anx

iety

Dep

ress

ion

Hal

luci

natio

n

Sexu

al

dysf

unct

ion

Falls

RL

S

Swea

ting

Wei

ght L

oss

98 53 M 1.5 30 1 y y y 99 57 F 2 36 1.5 y y y y y

100 64 M 12 106 4 y y y y y y y y y y y Y – yes

MASTER CHART


UPDRS Score

Hoehn & Yahr

stage

NON-MOTOR SYMPTOMS

Dro

olin

g

Tas

te /

Smel

l

Swal

low

Con

stip

atio

n

Urg

ency

Noc

turi

a

Diz

zine

ss

Pain

s

Dre

ams

Inso

nmia

Slee

pine

ss

Mem

ory

Anx

iety

Dep

ress

ion

Hal

luci

natio

n

Sexu

al

dysf

unct

ion

Falls

RL

S

Swea

ting

Wei

ght L

oss

1 56 M 5 49 3 Y y y y y y y y y y y y2 66 M 2 30 1.5 y y y y 3 59 M 1 27 1 y y y 4 65 M 2 23 2 y y y y y 5 69 F 4 42 1.5 y y y y y 6 60 F 9 52 3 y y y y y y y y y y 7 62 M 4 41 2 y y y y y y 8 60 M 2 25 1.5 y y y 9 53 M 2 52 3 y y y y y y y y y y 10 64 F 6 54 3 y y y y y y y y y y 11 54 M 2 29 1 y y y 12 51 F 2 30 1 y y y 13 65 M 4 44 2 y y y y y14 50 F 7 49 3 y y y y y y y y y y y15 52 F 4 52 2 y y y y y 16 46 M 2 51 3 y y y y y y y y y y y 17 52 F 8 44 2 y y y y 18 51 M 3 33 2 y y y y y 19 56 M 8 53 3 y y y y y y y y y y y 20 63 M 1 24 1 y y y 21 72 M 3 31 2 y y y y y y 22 55 M 2 46 2 y y y y y


UPDRS Score

Hoehn & Yahr

stage

NON-MOTOR SYMPTOMS

Dro

olin

g

Tas

te /

Smel

l

Swal

low

Con

stip

atio

n

Urg

ency

Noc

turi

a

Diz

zine

ss

Pain

s

Dre

ams

Inso

nmia

Slee

pine

ss

Mem

ory

Anx

iety

Dep

ress

ion

Hal

luci

natio

n

Sexu

al

dysf

unct

ion

Falls

RL

S

Swea

ting

Wei

ght L

oss

23 59 M 2 42 2 y y y y y 24 52 M 1 33 1 y y 25 55 M 1.5 27 1 y y y 26 60 F 3 27 1 y y y 27 67 M 5 49 2 y y y y 28 55 M 3 48 2 y y y y y 29 61 M 5 55 3 y y y y y y y y y 30 66 M 3 31 2 y y y 31 58 M 1 26 1 y y y 32 68 M 5 36 3 y y y y y y y y y y 33 60 M 6 45 3 y y y y y y y y y y 34 73 M 3 52 3 y y y y y y y y y y y y 35 72 M 1 32 2 y y y y 36 78 F 2 37 2 y y y y 37 55 F 1 29 1 y y 38 62 M 1.5 32 1 y y y 39 78 M 1.5 63 2 y y y y y 40 60 M 1 22 1 y y y 41 55 M 3 43 2.5 y y y y y 42 62 M 2 42 2 y y y y 43 68 M 15 68 3 y y y y y y y y y y y 44 62 M 9 50 2.5 y y y y y y 45 56 F 2 36 1.5 y y y y y 46 60 M 4 60 2 y y y y y y y y y 47 70 M 3 79 3 y y y y y y y y y y y


UPDRS Score

Hoehn & Yahr

stage

NON-MOTOR SYMPTOMS

Dro

olin

g

Tas

te /

Smel

l

Swal

low

Con

stip

atio

n

Urg

ency

Noc

turi

a

Diz

zine

ss

Pain

s

Dre

ams

Inso

nmia

Slee

pine

ss

Mem

ory

Anx

iety

Dep

ress

ion

Hal

luci

natio

n

Sexu

al

dysf

unct

ion

Falls

RL

S

Swea

ting

Wei

ght L

oss

48 77 M 8 81 3 y y y y y y y y y y y y 49 58 M 4 61 2.5 y y y y y y y 50 62 M 8 61 3 y y y y y y y y y y 51 60 M 7 48 2 y y y y y y y 52 58 M 2 32 1 y y y y y 53 68 M 3 33 2 y y y y 54 52 M 1 34 1 y y y y y 55 62 M 2 32 1 y y y y y y 56 57 M 5 70 3 y y y y y y y y y y y y 57 70 M 1 54 2 y y y y 58 54 M 1.5 34 1 y y y 59 55 M 1 51 2 y y y y y 60 65 M 15 67 2.5 y y y y y y 61 65 F 13 109 4 y y y y y y y y y y y 62 52 F 2 59 2 y y y y y y 63 69 M 10 78 3 y y y y y y y y y 64 58 M 1 24 1 y y 65 60 M 2 40 2 y y y y 66 63 M 1.5 30 1.5 y y y y 67 70 M 8 89 3 y y y y y y y y y y 68 62 F 5 36 2 y y y y y 69 55 M 4 52 2.5 y y y y y 70 53 M 2 26 1 y y y 71 60 F 9 80 3 y y y y y y y y y y y y 72 70 M 4 38 2 y y y y y


UPDRS Score

Hoehn & Yahr

stage

NON-MOTOR SYMPTOMS

Dro

olin

g

Tas

te /

Smel

l

Swal

low

Con

stip

atio

n

Urg

ency

Noc

turi

a

Diz

zine

ss

Pain

s

Dre

ams

Inso

nmia

Slee

pine

ss

Mem

ory

Anx

iety

Dep

ress

ion

Hal

luci

natio

n

Sexu

al

dysf

unct

ion

Falls

RL

S

Swea

ting

Wei

ght L

oss

73 56 M 3 40 2 y y y y y 74 58 F 12 122 4 y y y y y y y y y y y 75 54 M 1 24 1 y y y 76 66 M 2.5 40 2 y y y y 77 52 F 1 28 1 y y y 78 71 M 6 92 3 y y y y y y y y y 79 55 M 4 64 2.5 y y y y y 80 57 F 2 30 1.5 y y y y 81 64 M 2 42 2 y y y y 82 58 M 5 102 3 y y y y y y y y y y 83 76 M 3 48 2 y y y y 84 52 F 1 28 1 y y y 85 65 M 0.5 26 1 y y 86 59 M 2.5 44 2 y y y y y 87 60 M 4 98 3 y y y y y y y y y 88 62 M 14 126 4 y y y y y y y y y 89 64 M 1 40 2 y y y 90 67 F 3 48 2.5 y y y y y y 91 54 F 1 22 1 y y y y 92 70 F 8 110 3 y y y y y y y y y y y 93 52 M 2.5 32 2 y y y y 94 55 M 1 24 1 y y y 95 60 M 2 46 2 y y y y y 96 56 F 3 50 2.5 y y y y y y 97 58 M 3 48 2 y y y y y


UPDRS Score

Hoehn & Yahr

stage

NON-MOTOR SYMPTOMS

Dro

olin

g

Tas

te /

Smel

l

Swal

low

Con

stip

atio

n

Urg

ency

Noc

turi

a

Diz

zine

ss

Pain

s

Dre

ams

Inso

nmia

Slee

pine

ss

Mem

ory

Anx

iety

Dep

ress

ion

Hal

luci

natio

n

Sexu

al

dysf

unct

ion

Falls

RL

S

Swea

ting

Wei

ght L

oss

98 53 M 1.5 30 1 y y y 99 57 F 2 36 1.5 y y y y y

100 64 M 12 106 4 y y y y y y y y y y y Y – yes

Date post:	19-Dec-2020
Category:	Documents
Upload:	others
View:	3 times
Download:	0 times

THE TAMILNADU DR.M.G.R. MEDICAL UNIVERSITY · 2019. 11. 21. · like diplopia, fatigue and...

Documents